Adjuvant Chemotherapy Shows Strong Benefit in Upper Tract Urothelial Carcinoma

Alison J. Birtle, MD, MBBS, MRCP, FRCR

Adjuvant platinum-based chemotherapy reduced the risk of disease recurrence or death by 55% in patients with upper tract urothelial carcinoma (UTUC), according to findings from the phase III POUT trial that have now been published in The Lancet.

At a median follow-up of 30.3 months, the median disease-free survival (DFS) was not reached in patients receiving adjuvant chemotherapy compared with 29.8 months in patients randomized to surveillance (HR, 0.45; 95% CI, 0.30-0.68; P = .0001). The 3-year DFS estimates were 71% (95% CI, 61-78) versus 46% (95% CI, 36-56), respectively.

Adjuvant chemotherapy also reduced the risk of metastasis or death by 52% (HR, 0.48; 95% CI, 0.31-0.74; P = .0007). The 3-year event-free rates were 71% versus 53% in the chemotherapy and surveillance arms, respectively.

“Gemcitabine/platinum combination chemotherapy initiated within 90 days after nephroureterectomy significantly improved disease-free survival in patients with locally advanced UTUC. Adjuvant platinum-based chemotherapy should be considered a new standard of care after nephroureterectomy for this patient population,” lead study investigator Alison J. Birtle, MD, MBBS, MRCP, FRCR, a consultant clinical oncologist for Lancashire Teaching Hospitals, NHS Foundation Trust in the United Kingdom, wrote in their study conclusion.

The multicenter phase III POUT trial randomized patients to receive either chemotherapy (n = 131) or surveillance (n = 129). Eligible patients had UTUC stage pT2 to pT4 disease, with pN0, M0, or pTany N1 to N3 nodal status, provided that abnormal nodes were resected at surgery. They also had to have a World Health Organization performance status of 0 or 1, without distant metastases, and a glomerular filtration rate (GFR) of greater than 30 mL/min. Patients who had concurrent MIBC were excluded from the trial, but patients with nonmuscle invasive bladder cancer were accepted.

Patients in the chemotherapy group were administered 4 cycles of adjuvant chemotherapy delivered within 90 days of their nephroureterectomy and were further stratified to receive gemcitabine with either cisplatin or carboplatin based on their renal function. Patients who had suboptimal renal function (GFR 30-49 mL/min) received carboplatin instead of cisplatin. the primary endpoint was DFS, and the secondary endpoint was MFS. Patient characteristics were mostly balanced between the 2 arms in terms of age group, sex, pathological stage, and nodal involvement.

The safety population for the chemotherapy arm included 126 patients, 44% (n = 55) of whom had acute grade ≥3 treatment-emergent adverse events. In the surveillance arm, 5 (4%) of 129 patients had acute grade 3 or worse emergent events. There were no treatment related deaths.

“To the best of our knowledge, our study is the largest randomized controlled clinical trial done exclusively in patients with UTUC worldwide,” Birtle et al wrote. “Future studies should focus on combinations with novel agents in the adjuvant setting, which might further improve the prognosis for locally advanced UTUC.”

Birtle A, Johnson M, Chester J, et al. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial [published online March 5, 2020]. Lancet. https://doi.org/10.1016/ S0140-6736(20)30415-3